simeprevir 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
Hepatitis Virus C (HVC) protease inhibitors 4812 923604-59-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • olysio
  • TMC-435
  • TMC435350
  • simeprevir
  • simeprevir sodium
Oral HCV-PROTEASE INHIBITOR effective against hepatitis C virus (HCV) serine protease NS3/4A. It is used in the treatment of chronic hepatitis C (Antivirals) genotype 1 infection in adults with compensated liver disease, including CIRRHOSIS.
  • Molecular weight: 749.94
  • Formula: C38H47N5O7S2
  • CLOGP: 5.45
  • LIPINSKI: 3
  • HAC: 12
  • HDO: 2
  • TPSA: 156.89
  • ALOGS: -5.39
  • ROTB: 7

  • Status: OFM

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.15 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Hosey CM, Chan R, Benet LZ

Approvals:

DateAgencyCompanyOrphan
May 14, 2014 EMA
Nov. 22, 2013 FDA JANSSEN PRODS

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Platelet count decreased 773.97 36.36 301 4456 106082 56181228
Anaemia 573.80 36.36 325 4432 267186 56020124
White blood cell count decreased 464.65 36.36 221 4536 125769 56161541
Blood bilirubin increased 388.10 36.36 134 4623 33220 56254090
Hepatitis C 290.98 36.36 72 4685 5514 56281796
Neutrophil count decreased 277.54 36.36 117 4640 49705 56237605
Haemoglobin decreased 217.43 36.36 137 4620 134000 56153310
Hyperbilirubinaemia 166.27 36.36 53 4704 10182 56277128
Haemolytic anaemia 148.49 36.36 48 4709 9637 56277673
Hepatocellular carcinoma 105.47 36.36 27 4730 2362 56284948
Pruritus 101.79 36.36 129 4628 316494 55970816
Off label use 94.57 36.36 168 4589 556012 55731298
Pyrexia 91.90 36.36 142 4615 418631 55868679
Photosensitivity reaction 85.86 36.36 35 4722 13558 56273752
Remission not achieved 51.97 36.36 9 4748 113 56287197
Decreased appetite 45.94 36.36 73 4684 219158 56068152
Hepatic failure 43.74 36.36 30 4727 33456 56253854
Hepatic function abnormal 42.88 36.36 30 4727 34528 56252782
Jaundice 41.79 36.36 27 4730 27267 56260043
Hepatic encephalopathy 40.82 36.36 19 4738 10091 56277219
Sunburn 40.44 36.36 13 4744 2555 56284755
Hepatitis C RNA increased 37.55 36.36 7 4750 136 56287174
Pain 36.90 36.36 6 4751 663178 55624132

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hepatitis C 769.03 29.92 207 5476 10423 31681238
Platelet count decreased 542.28 29.92 300 5383 110135 31581526
White blood cell count decreased 391.37 29.92 224 5459 87174 31604487
Blood bilirubin increased 352.96 29.92 156 5527 34980 31656681
Anaemia 306.54 29.92 273 5410 213249 31478412
Hepatocellular carcinoma 240.55 29.92 81 5602 8675 31682986
Off label use 193.76 29.92 271 5412 347003 31344658
Hyperbilirubinaemia 170.95 29.92 74 5609 15676 31675985
Haemoglobin decreased 144.73 29.92 136 5547 112539 31579122
Neutrophil count decreased 142.91 29.92 94 5589 46300 31645361
Photosensitivity reaction 139.30 29.92 56 5627 9848 31681813
Drug ineffective 90.62 29.92 210 5473 395363 31296298
Jaundice 73.38 29.92 53 5630 30234 31661427
Remission not achieved 71.07 29.92 13 5670 100 31691561
Pruritus 67.92 29.92 97 5586 125070 31566591
Haemolytic anaemia 59.83 29.92 31 5652 9765 31681896
Sunburn 51.50 29.92 17 5666 1703 31689958
Treatment failure 47.89 29.92 47 5636 40745 31650916
Hepatic failure 46.68 29.92 42 5641 32660 31659001
Genotype drug resistance test positive 45.88 29.92 14 5669 1087 31690574
Pyrexia 44.43 29.92 137 5546 303703 31387958
Viral load increased 43.74 29.92 16 5667 2173 31689488
Hepatitis C RNA increased 42.86 29.92 10 5673 274 31691387
Hepatic encephalopathy 42.71 29.92 28 5655 13643 31678018
Ascites 42.19 29.92 44 5639 40969 31650692
Thought blocking 38.68 29.92 8 5675 123 31691538
Bilirubin conjugated increased 38.13 29.92 16 5667 3125 31688536
Rash 34.27 29.92 96 5587 201390 31490271
Choroiditis 33.13 29.92 11 5672 1121 31690540
Hyperuricaemia 32.84 29.92 19 5664 7419 31684242

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Platelet count decreased 1363.06 30.23 600 9114 177622 70741108
Hepatitis C 940.26 30.23 239 9475 12568 70906162
White blood cell count decreased 897.17 30.23 444 9270 169697 70749033
Anaemia 855.84 30.23 581 9133 402842 70515888
Blood bilirubin increased 692.15 30.23 272 9442 59629 70859101
Neutrophil count decreased 414.53 30.23 210 9504 83346 70835384
Haemoglobin decreased 365.24 30.23 267 9447 204892 70713838
Hepatocellular carcinoma 346.11 30.23 104 9610 10104 70908626
Hyperbilirubinaemia 315.56 30.23 118 9596 22450 70896280
Haemolytic anaemia 202.99 30.23 79 9635 16715 70902015
Pruritus 153.12 30.23 211 9503 345349 70573381
Photosensitivity reaction 139.49 30.23 63 9651 19277 70899453
Pyrexia 136.64 30.23 273 9441 606679 70312051
Jaundice 109.07 30.23 74 9640 50034 70868696
Remission not achieved 104.54 30.23 21 9693 369 70918361
Off label use 89.84 30.23 263 9451 742797 70175933
Hepatic failure 84.38 30.23 67 9647 57558 70861172
Hepatic encephalopathy 66.32 30.23 40 9674 22078 70896652
Hepatitis C RNA increased 63.47 30.23 14 9700 392 70918338
Bilirubin conjugated increased 61.25 30.23 24 9690 5157 70913573
Rash 59.80 30.23 179 9535 510383 70408347
Pain 59.43 30.23 8 9706 628808 70289922
Ascites 56.01 30.23 57 9657 67490 70851240
Hyperuricaemia 55.45 30.23 28 9686 10938 70907792
Sunburn 54.73 30.23 20 9694 3551 70915179
Decreased appetite 53.10 30.23 124 9590 304656 70614074
Insomnia 47.45 30.23 97 9617 217709 70701021
Malaise 47.08 30.23 148 9566 432784 70485946
Hepatorenal syndrome 45.61 30.23 18 9696 3939 70914791
Aspartate aminotransferase increased 45.01 30.23 70 9644 126908 70791822
Hepatic function abnormal 41.76 30.23 49 9665 67947 70850783
Red blood cell count decreased 41.39 30.23 43 9671 52118 70866612
Hepatic cirrhosis 41.29 30.23 34 9680 30697 70888033
Thought blocking 37.53 30.23 8 9706 190 70918540
Viral load increased 37.48 30.23 14 9700 2642 70916088
Choroiditis 34.54 30.23 11 9703 1290 70917440
Liver disorder 33.93 30.23 42 9672 61526 70857204
Alanine aminotransferase increased 32.46 30.23 66 9648 147414 70771316
Injection site dermatitis 31.64 30.23 5 9709 19 70918711
Incorrect product administration duration 30.96 30.23 19 9695 10805 70907925

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC J05AP05 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HCV infections
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000998 Antiviral Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D011480 Protease Inhibitors
FDA MoA N0000182138 Cytochrome P450 1A2 Inhibitors
FDA MoA N0000182141 Cytochrome P450 3A4 Inhibitors
FDA MoA N0000182638 HCV NS3/4A Protease Inhibitors
FDA EPC N0000182639 Hepatitis C Virus NS3/4A Protease Inhibitor
FDA MoA N0000185503 P-Glycoprotein Inhibitors
FDA MoA N0000190107 Organic Anion Transporting Polypeptide 1B1 Inhibitors
FDA MoA N0000190108 Organic Anion Transporting Polypeptide 1B3 Inhibitors
FDA MoA N0000190113 Breast Cancer Resistance Protein Inhibitors
FDA MoA N0000193845 Bile Salt Export Pump Inhibitors
FDA MoA N0000193960 Multidrug Resistance-Associated Protein 2 Inhibitors
FDA MoA N0000193965 Sodium Taurocholate Co-transporting Polypeptide Inhibitors

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Chronic hepatitis C indication 128302006




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 4.35 acidic
pKa2 6.66 Basic
pKa3 3.5 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 8349869 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 8741926 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 8754106 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 9040562 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 9353103 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 9623022 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 9856265 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 8148399 Sept. 5, 2029 METHOD OF TREATING HEPATITIS C

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Cathepsin S Enzyme IC50 6.10 CHEMBL
Hepatitis C virus serine protease, NS3/NS4A Enzyme INHIBITOR Ki 9.30 CHEMBL CHEMBL
Genome polyprotein Polyprotein INHIBITOR Ki 9.44 SCIENTIFIC LITERATURE DRUG LABEL
Polyprotein Polyprotein INHIBITOR Ki 9.44 IUPHAR
Nonstructural protein NS3-4A Unclassified Ki 9.44 CHEMBL
Genome polyprotein Unclassified Ki 9.30 CHEMBL

External reference:

IDSource
D10081 KEGG_DRUG
4032900 VANDF
CHEBI:134743 CHEBI
30B PDB_CHEM_ID
CHEMBL501849 ChEMBL_ID
7367 IUPHAR_LIGAND_ID
9432 INN_ID
1241946-89-3 SECONDARY_CAS_RN
DB06290 DRUGBANK_ID
9WS5RD66HZ UNII
1482790 RXNORM
207569 MMSL
29896 MMSL
d08182 MMSL
015309 NDDF
015310 NDDF
708823009 SNOMEDCT_US
714167009 SNOMEDCT_US
C2605855 UMLSCUI
D000069616 MESH_DESCRIPTOR_UI
CHEMBL3137358 ChEMBL_ID
24873435 PUBCHEM_CID

Pharmaceutical products:

None